Phenyl-dihydropyridine derivatives as inhibitors of aldosterone synthase

1. A compound of formula (I)

wherein

R 1 , R 2 R 4 and R 5 are independently selected from H, halogen, cyano, nitro, alkyl, haloalkyl, cycloalkyl, alkoxy, haloalkoxy and cycloalkoxy;

R 3 is haloalkyl;

R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are independently selected from H, halogen, alkyl and haloalkyl;

R 12 is H, alkyl, haloalkyl, cycloalkyl, substituted aryl or substituted heteroaryl, wherein substituted aryl or substituted heteroaryl are substituted with R 18 , R 19 and R 20 ;

A 1 is —(CR 14 R 15 ) p —NR 16 R 17 , —(CR 14 R 15 ) p —OR 17 , —(CR 14 R 15 ) p —C(O)NR 16 R 17 or —(CR 14 R 15 ) p —C(O)OR 17 ;

R 14 and R 15 are independently selected from H, alkyl, haloalkyl, cycloalkyl and halocycloalkyl;

R 16 is H, alkyl, haloalkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl or haloalkoxyalkyl;

R 17 is H, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, cycloalkoxyalkyl, substituted aryl or substituted heteroaryl, wherein substituted aryl and substituted heteroaryl are substituted with R 21 , R 22 and R 23 ;

or R 16 and R 17 together with the nitrogen to which they are attached form a substituted heterocycloalkyl or a substituted heteroaryl, wherein substituted heterocycloalkyl and substituted heteroaryl are substituted with R 21 , R 22 and R 23 ;

R 18 , R 19 , R 20 , R 21 , R 22 and R 23 are independently selected from H, halogen, alkyl, haloalkyl, cycloalkyl, alkoxy and haloalkoxy;

n is zero, 1 or 2;

p is zero, 1 or 2;

and pharmaceutically acceptable salts thereof.

2. The compound of claim 1 , wherein R 1 , R 2 , R 4 and R 5 are independently selected from H, halogen and haloalkyl.

3. The compound of claim 1 , wherein R 1 and R 2 are independently selected from H and halogen.

4. The compound of claim 1 , wherein R 4 and R 5 are H.

5. The compound of claim 1 , wherein n is zero and R 6 , R 7 , R 8 and R 9 are H.

6. The compound of claim 1 , wherein R 12 is H, alkyl or substituted aryl, wherein substituted aryl is substituted with R 18 , R 19 and R 20 .

7. The compound of claim 1 , wherein R 18 , R 19 and R 20 are H.

8. The compound of claim 1 , wherein A 1 is —(CR 14 R 15 ) p —OR 17 or —(CR 14 R 15 ) p —C(O)NR 16 R 17 .

9. The compound of claim 1 , wherein A 1 is —(CR 14 R 15 ) p —OR 17 .

10. The compound of claim 1 , wherein R 16 is H.

11. The compound of claim 1 , wherein R 17 is H, alkyl, alkoxyalkyl or substituted heteroaryl, wherein substituted heteroaryl is substituted with R 21 , R 22 and R 23 or R 16 and R 17 together with the nitrogen to which they are attached form a substituted heterocycloalkyl, wherein substituted heterocycloalkyl is substituted with R 21 , R 22 and R 23 .

12. The compound of claim 1 , wherein R 17 is H, alkyl, alkoxyalkyl or substituted heteroaryl, wherein substituted heteroaryl is substituted with R 21 , R 22 and R 23 .

13. The compound of claim 1 , wherein R 21 , R 22 and R 23 are independently selected from H and alkyl.

14. The compound of claim 1 , wherein R 14 and R 15 are H.

15. The compound of claim 1 , wherein p is zero or 1.

16. A compound selected from

4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-amine;

4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

4-(3-fluoro-4-(trifluoromethyl)phenyl)-5-methyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

4-(3-fluoro-4-(trifluoromethyl)phenyl)-5-phenyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-methyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-isopropyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-phenyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

(+)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-phenyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

(+4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-phenyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

(R)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-phenyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

(S)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-5-phenyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ol;

ethyl 2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)acetate;

2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-N-methylacetamide;

N-(cyclopropylmethyl)-2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)acetamide;

2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-N-propylacetamide;

2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-1-(piperidin-1-yl)ethanone;

2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-1-morpholinoethanone;

2-[4-(3-Fluoro-4-trifluoromethyl-phenyl)-6,7-dihydro-5H-[2]pyrindin-5-yl]-N-isoxazol-3-yl-acetamide;

2-(4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-N-(1H-pyrazol-3-yl)acetamide;

2-(4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-1-(pyrrolidin-1-yl)ethanone;

N-ethyl-2-(4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-N-methylacetamide;

2-(4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-N-isopropyl-N-methylacetamide;

N-cyclopropyl-2-(4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-N-methylacetamide;

N-cyclopropyl-N-ethyl-2-(4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)acetamide;

2-(4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-yl)-1-((S)-2-methylpyrrolidin-1-yl)ethanone;

and pharmaceutically acceptable salts thereof.

17. A process to prepare a compound of claim 1 comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III);

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , n and p are as defined herein, R 24 is alkyl and A 1 is —(CR 14 R 15 )—C(O)NR 16 R 17 .

18. A pharmaceutical composition comprising a compound of claim 1 and a therapeutically inert carrier.

19. A method for the treatment or prophylaxis chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrom, which method comprises administering an effective amount of a compound of claim 1 to a subject in need thereof.